A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases

Neurosci Lett. 1999 Dec 24;277(2):123-6. doi: 10.1016/s0304-3940(99)00865-4.


A recent report has shown that Wolfram syndrome carriers (heterozygotes) are 26-fold more likely to require psychiatric hospitalization compared with non-carriers, and that Wolfram syndrome heterozygotes may constitute approximately 25% of individuals hospitalized with depression and suicide attempts. We analyzed a His611Arg polymorphism of the wolframin gene by the polymerase chain reaction (PCR) and HhaI restriction digestion, in 158 bipolar I and 163 unipolar major affective disorder cases, and 316 controls. Statistical analyses of allele or genotype frequencies do not support a major role for wolframin in affective disorder. HhaI restriction digestion and sequencing of PCR products from four affective disorder cases showed a heterozygous Ala559Thr change. The Ala559Thr variant was not detectable in 382 controls tested. Thus, the rare wolframin 559Thr allele deserves consideration as a risk allele for affective disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Bipolar Disorder / genetics*
  • Codon / genetics
  • Depressive Disorder / genetics*
  • Female
  • Genetic Carrier Screening
  • Genotype
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mood Disorders / genetics
  • Polymorphism, Genetic / genetics*
  • Wolfram Syndrome / genetics*


  • Codon
  • Membrane Proteins
  • wolframin protein